Methadone for Pain Management in Cardiac Surgery

Overseen By Anesthesia Clinical Research Unit

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: Mayo Clinic

Must not be taking: Opioids

Disqualifiers: Chronic pain, Opioid use disorder, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 5 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

40 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

The purpose of this study is to compare the effects of administration of oral methadone preoperatively and intravenous methadone upon induction of general anesthesia on postoperative pain for patients undergoing elective cardiac surgery.

Do I need to stop taking my current medications for the trial?

The trial information does not specify if you need to stop taking your current medications. However, if you have chronic pain requiring opioid medications or are on medication-assisted treatment for opioid use disorder, you cannot participate.

Is methadone safe for use in cardiac surgery pain management?

Methadone has been studied for pain management in cardiac surgery and is generally considered safe, with no significant difference in side effects compared to other opioids. However, caution is advised due to potential risks like prolonged QT interval (a heart rhythm issue) at high doses. ^{1 2 3 4 5}

How is the drug methadone unique for pain management in cardiac surgery?

Methadone is unique for pain management in cardiac surgery because it can be given intravenously during surgery to reduce the need for other opioids afterward, helping to manage pain more effectively and potentially improving recovery without increasing side effects. ^{1 5 6 7 8}

What data supports the effectiveness of the drug methadone for pain management in cardiac surgery?

Research shows that using methadone during surgery can reduce the need for other pain medications like morphine in the first 24 hours after cardiac surgery, although it may not lower pain scores directly. Methadone has been found to provide effective pain relief and reduce overall opioid consumption without increasing side effects compared to other opioids. ^{1 3 5 6 8}

Who Is on the Research Team?

Krishnan Ramanujan

Principal Investigator

Mayo Clinic

Are You a Good Fit for This Trial?

This trial is for patients scheduled for elective cardiac surgery who need pain management. Specific eligibility criteria are not provided, but typically participants must be adults in stable condition without conflicting health issues or medications that could interfere with the study.

Inclusion Criteria

I am scheduled for heart surgery first thing in the morning.

Exclusion Criteria

I need opioid painkillers for my chronic pain.

Intolerance to methadone

Opioid use disorder on medication assistance treatment

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Preoperative Treatment

Participants receive oral methadone immediately prior to transport for surgery

Immediate

Intraoperative Treatment

Participants receive intravenous methadone upon induction of general anesthesia

During surgery

Postoperative Monitoring

Participants' pain scores are monitored at various intervals after extubation

72 hours

Follow-up

Participants are monitored for safety and effectiveness after treatment

1-2 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Methadone

Trial Overview The study aims to compare two ways of managing pain: taking methadone by mouth before being moved for surgery versus getting it through a vein when general anesthesia starts. The goal is to see which method better controls postoperative pain.

How Is the Trial Designed?

Group I: Oral methadone, immediately prior to transport Experimental Treatment 1 Intervention

Group II: Intravenous methadone Active Control 1 Intervention

Methadone is already approved in United States, European Union, Canada, Japan, Switzerland for the following indications:

Approved in United States as Dolophine for:

• Pain management
• Opioid use disorder

Approved in European Union as Methadose for:

• Pain management
• Opioid dependence

Approved in Canada as Physeptone for:

• Pain management
• Opioid use disorder

Approved in Japan as Heptadon for:

• Pain management

Approved in Switzerland as Heptanon for:

• Pain management
• Opioid dependence

Who Is Running the Clinical Trial?

Mayo Clinic

Lead Sponsor

Trials

3,427

Recruited

3,221,000+

Published Research Related to This Trial

Intravenous methadone has been shown to provide effective postoperative pain relief and reduce the need for other opioids, with a similar safety profile to other opioid analgesics, based on a review of multiple studies.

While there is promising evidence for the use of intravenous methadone in managing chronic cancer pain, more research is needed to fully understand its efficacy in this area.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intravenous Methadone for Perioperative and Chronic Cancer Pain: A Review of the Literature. Mercadante, S.[2023]

A study of 39 patients undergoing opioid rotation from methadone to alternative opioids found that the mean dose ratio for oral methadone to oral morphine equivalent daily dose was 1:4.7, and for intravenous methadone, it was 1:13.5, indicating significant differences in potency between the two forms.

The research suggests that these new dose ratios can help clinicians switch patients to alternative opioids more safely, especially when managing side effects or inadequate pain control from methadone.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Switching from methadone to a different opioid: what is the equianalgesic dose ratio? Walker, PW., Palla, S., Pei, BL., et al.[2018]

Methadone is a unique opioid that not only acts on mu receptors but also has effects on delta receptors and NMDA receptors, making it a complex option for pain management, especially in cases of uncontrolled pain or when other opioids cause toxicity.

While methadone can be safer at lower doses, there are significant risks associated with high doses, including prolonged QT interval and potential for serious heart issues, highlighting the need for more research through randomized controlled trials to better understand its safety and efficacy compared to other opioids.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Methadone for treatment of cancer pain. Bryson, J., Tamber, A., Seccareccia, D., et al.[2019]

Citations

1. England pubmed.ncbi.nlm.nih.gov

Intraoperative Methadone Use in Cardiac Surgery: A Systematic Review. [2022]

2. United States pubmed.ncbi.nlm.nih.gov

Preoperative oral methadone for postoperative pain in patients undergoing cardiac surgery: A randomized double-blind placebo-controlled pilot. [2022]

3. England pubmed.ncbi.nlm.nih.gov

Impact of intraoperative methadone use on postoperative opioid requirements after cardiac surgery. [2022]

4. United States pubmed.ncbi.nlm.nih.gov

Intraoperative Methadone for the Prevention of Postoperative Pain: A Randomized, Double-blinded Clinical Trial in Cardiac Surgical Patients. [2022]

5. New Zealand pubmed.ncbi.nlm.nih.gov

Intravenous Methadone for Perioperative and Chronic Cancer Pain: A Review of the Literature. [2023]

6. United States pubmed.ncbi.nlm.nih.gov

Switching from methadone to a different opioid: what is the equianalgesic dose ratio? [2018]

7. United States pubmed.ncbi.nlm.nih.gov

Methadone for treatment of cancer pain. [2019]

8. France pubmed.ncbi.nlm.nih.gov

The effect of intraoperative methadone during pediatric cardiac surgery on postoperative opioid requirements. [2021]